Analysis of the microglia transcriptome across the human lifespan using single cell RNA sequencing

Yaqubi, Moein; Groh, Adam M.R.; Dorion, Marie‐France; Afanasiev, Elia; Luo, Julia Xiao Xuan; Hashemi, Hadi; Sinha, Sarthak; Kieran, Nicholas W.; Blain, Manon; Cui, Qiao‐Ling; Biernaskie, Jeff; Srour, Myriam; Dudley, Roy; Hall, Jeffery A.; Sonnen, Joshua A.; Arbour, Nathalie; Prat, Alexandre; Stratton, Jo Anne; Antel, Jack P.; Healy, Luke M.

doi:10.1186/s12974-023-02809-7

Cited by 9 publications

(4 citation statements)

References 55 publications

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“…Consistent with prior studies, we observed significant microglial heterogeneity in fetal brains 34,35,98 . Not surprisingly, the microglial clusters with the more robust yolk sac signature also highly express genes known to be associated with another yolk sac-derived tissue resident brain macrophage population, CNS-associated macrophages (CAMs) 99–101 .…”

Section: Discussionsupporting

confidence: 92%

Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity

Batorsky,

Ceasrine,

Shook

et al. 2023

Preprint

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SummaryMaternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many mediated by in utero microglial programming. As microglia remain inaccessible throughout development, identification of noninvasive biomarkers reflecting fetal brain microglial programming could permit screening and intervention. We used lineage tracing to demonstrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells) in a mouse model of maternal diet-induced obesity, and single-cell RNA-seq to demonstrate shared transcriptional programs. Comparison with human datasets demonstrated conservation of placental resident macrophage signatures between mice and humans. Single-cell RNA-seq identified common alterations in fetal microglial and Hofbauer cell gene expression induced by maternal obesity, as well as sex differences in these alterations. We propose that Hofbauer cells, which are easily accessible at birth, provide novel insights into fetal brain microglial programs, and may facilitate the early identification of offspring vulnerable to neurodevelopmental disorders in the setting of maternal exposures.

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Section: Discussionsupporting

confidence: 92%

Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity

Batorsky,

Ceasrine,

Shook

et al. 2023

Preprint

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show abstract

“…To further emphasize the importance of considering species-specific factors in understanding microglial development, a recent study employed principal component analysis and batch effect verification techniques to comprehensively analyze the developmental transcriptomes of human and mouse microglia [ 213 ]. The study investigated potential species-specific differences in microglial maturation, highlighting the significance of species-related factors in this process.…”

Section: Introductionmentioning

confidence: 99%

“…Notably, in mouse pups, microglia formed a separate cluster distinct from their juvenile and adult counterparts, whereas human pediatric microglia were closely grouped with adult and adolescent samples. Based on the observed discrepancy, the researchers posited the hypothesis that mouse pediatric microglia might experience a developmental delay in maturation relative to their human counterparts [ 213 ].…”

Section: Introductionmentioning

confidence: 99%

Microglial contribution to the pathology of neurodevelopmental disorders in humans

Matuleviciute,

Akinluyi,

Muntslag

et al. 2023

Acta Neuropathol

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Microglia are the brain’s resident macrophages, which guide various developmental processes crucial for brain maturation, activity, and plasticity. Microglial progenitors enter the telencephalic wall by the 4th postconceptional week and colonise the fetal brain in a manner that spatiotemporally tracks key neurodevelopmental processes in humans. However, much of what we know about how microglia shape neurodevelopment comes from rodent studies. Multiple differences exist between human and rodent microglia warranting further focus on the human condition, particularly as microglia are emerging as critically involved in the pathological signature of various cognitive and neurodevelopmental disorders. In this article, we review the evidence supporting microglial involvement in basic neurodevelopmental processes by focusing on the human species. We next concur on the neuropathological evidence demonstrating whether and how microglia contribute to the aetiology of two neurodevelopmental disorders: autism spectrum conditions and schizophrenia. Next, we highlight how recent technologies have revolutionised our understanding of microglial biology with a focus on how these tools can help us elucidate at unprecedented resolution the links between microglia and neurodevelopmental disorders. We conclude by reviewing which current treatment approaches have shown most promise towards targeting microglia in neurodevelopmental disorders and suggest novel avenues for future consideration.

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“…Interestingly, scRNAseq on human microglia isolated from pre-natal (2nd trimester), pediatric (18 months – 24 months), adolescent (10-14 years old), and adult (40-62 years old) brain samples revealed pre-natal microglia with a higher phagocytic activity (i.e., upregulation of CD36 , TREM2 , and FCGR1B ) compared to those at an adult stage. Adult microglia, however, were more immune responsive (i.e., upregulation of the pro-inflammatory cytokines IL18 and CX3CR4 , the interferon-response genes CCL3 and CCL4 as well as SPP1 , IL1B , and MSR1 ) ( 142 ) ( Figure 4 ). Likewise, microglia from patients aged 50 years and older had higher SPP1 expression levels compared to microglia from younger adults ( 143 ) ( Figure 4 ).…”

Section: Lessons Learned From Microglia Transcriptomicsmentioning

confidence: 99%

The ins and outs of microglial cells in brain health and disease

Pallarés-Moratalla,

Bergers

2024

Front. Immunol.

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Microglia are the brain’s resident macrophages that play pivotal roles in immune surveillance and maintaining homeostasis of the Central Nervous System (CNS). Microglia are functionally implicated in various cerebrovascular diseases, including stroke, aneurysm, and tumorigenesis as they regulate neuroinflammatory responses and tissue repair processes. Here, we review the manifold functions of microglia in the brain under physiological and pathological conditions, primarily focusing on the implication of microglia in glioma propagation and progression. We further review the current status of therapies targeting microglial cells, including their re-education, depletion, and re-population approaches as therapeutic options to improve patient outcomes for various neurological and neuroinflammatory disorders, including cancer.

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Analysis of the microglia transcriptome across the human lifespan using single cell RNA sequencing

Cited by 9 publications

References 55 publications

Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity

Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity

Microglial contribution to the pathology of neurodevelopmental disorders in humans

The ins and outs of microglial cells in brain health and disease

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